Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
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Authors
Ecker, S
Chen, L
Pancaldi, V
Bagger, FO
Fernández, JM
Carrillo de Santa Pau, E
Juan, D
Mann, AL
Watt, S
Casale, FP
Sidiropoulos, N
Rapin, N
Merkel, A
BLUEPRINT Consortium,
Stunnenberg, HG
Stegle, O
Pastinen, T
Kuijpers, TW
Rico, D
Valencia, A
Beck, S
Publication Date
2017-01-26Journal Title
Genome Biology
ISSN
1474-7596
Publisher
BioMed Central
Volume
18
Number
18
Language
English
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Ecker, S., Chen, L., Pancaldi, V., Bagger, F., Fernández, J., Carrillo de Santa Pau, E., Juan, D., et al. (2017). Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biology, 18 (18)https://doi.org/10.1186/s13059-017-1156-8
Abstract
Background
A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.
Results
We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14$^{+}$CD16$^{−}$ monocytes, CD66b$^{+}$CD16$^{+}$ neutrophils, and CD4$^{+}$CD45RA$^{+}$ naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers.
Conclusions
Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability.
Keywords
DNA methylation, differential variability, gene expression, heterogeneity, immune cells, monocytes, neutrophils, phenotypic plasticity, T cells
Sponsorship
This work is predominantly funded by the EU-FP7 Project BLUEPRINT (HEALTH-F5-2011-282510). S. Ecker is supported by a “la Caixa” pre-doctoral fellowship. V. Pancaldi is supported by a FEBS Long-Term Fellowship. F.O. Bagger is supported by The Lundbeck Foundation. K. Downes is funded as a HSST trainee by NHS Health Education England. M. Frontini is supported by the British Heart Foundation (BHF) Cambridge Centre of Excellence (RE/13/6/30180). S. Beck acknowledges support from the Wellcome Trust (WT99148), a Royal Society Wolfson Research Merit Award (WM100023), and the UK National Institute for Health Research (NIHR) UCLH Biomedical Research Centre (BRC84/CN/SB/5984). N. Soranzo’s research is supported by the Wellcome Trust (WT098051 and WT091310), EPIGENESYS (257082), and NIHR Cambridge Biomedical Research Centre (BRC). The INB-CNIO Unit is a member of ProteoRed (PRB2-ISCIII) and is supported by PE I + D + i 2013–2016 (PT13/0001), ISCIII, and FEDER. The Cardiovascular Epidemiology Unit is supported by the UK Medical Research Council (G0800270), BHF (SP/09/002), and NIHR Cambridge BRC.
Funder references
MRC (G0800270)
MRC (MR/L003120/1)
EC FP7 NOE (257082)
Wellcome Trust (091310/Z/10/Z)
British Heart Foundation (RG/08/014/24067)
British Heart Foundation (RE/13/6/30180)
British Heart Foundation (RG/13/13/30194)
Identifiers
External DOI: https://doi.org/10.1186/s13059-017-1156-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263195
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International